Synthesis and in vitro activity of dicationic indolyl diphenyl ethers as novel potent antibiotic agents against drug-resistant bacteria

Bioorg Med Chem Lett. 2017 Feb 15;27(4):841-844. doi: 10.1016/j.bmcl.2017.01.019. Epub 2017 Jan 10.

Abstract

A series of 4,4'-bis-[2-(6-N-substituted-amidino)indolyl] diphenyl ether have been synthesized and tested for their in vitro antibacterial activity including a range of Gram-positive and Gram-negative pathogens and cytotoxicity. Most of these compounds have mainly shown anti-Gram positive bacteria activities especially against drug resistant bacterial strains MRSA, MRSE and VRE. The anti-MRSA and anti-MRSE activities of compound 7a and 7j were more potent than that of the lead compound 2, levofloxacin and vancomycin. Interestingly, 7j had greatly improved anti negative bacterial activity, especially for the producing NDM-1 Klebsiella pneumonia strain and less toxic than that of the lead compound 2.

Keywords: Antibacterials; Diamidines; Indole; MRSA; VRE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Drug Resistance, Bacterial / drug effects
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Phenyl Ethers / chemical synthesis
  • Phenyl Ethers / chemistry*
  • Phenyl Ethers / pharmacology
  • Structure-Activity Relationship
  • Vancomycin Resistance / drug effects

Substances

  • Anti-Bacterial Agents
  • Phenyl Ethers